Research Summary

Michelle's lab develops innovative approaches to screen for chemical tools and drug leads, using biophysical approaches like fragment-based drug discovery and biological approaches including high-content imaging with primary cells and organisms. Our goal is to demonstrate 'druggability' of new target classes and to use our compounds to discover new targets for drug discovery. Areas of interest include protein-protein interactions, allosteric and scaffolding sites in enzymes, and orphan and neglected diseases. Michelle is co-Director of the Small Molecule Discovery Center, a collaborative research facility that includes high-throughput screening and medicinal chemistry (smdc.ucsf.edu). The SMDC is a Cancer Center Core.

Research Funding

  • July 1, 2020 - June 30, 2024 - Discovery of Small Molecule Ligands for PHD1 Reader Domain of Histone Demethylase KDM5A , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA250459
  • September 5, 2018 - July 31, 2022 - Protein and small-molecule tools to probe the conformational dependence of the VCP/p97 protein-protein interaction network , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM130145
  • June 1, 2021 - May 31, 2022 - Bruker Sierra SPR-24 Pro , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10OD030265
  • March 23, 2016 - February 29, 2020 - A high content screen dissecting ciliogenesis and oncogenic Hedgehog signaling , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA181231

Education

1990, Bryn Mawr College, Bryn Mawr, PA, B.A., Chemistry
1997, California Institute of Technology, Pasadena, CA, Ph.D., Chemistry
1999, Genentech, Inc, South San Francisco, CA and Sunesis Pharmaceuticals, Redwood City, CA, Postdoctoral fellowship, Protein Engineering

Honors & Awards

  • 1991
    European Traveling Fellowship, Bryn Mawr College
  • 1991-1992
    Blodgett Fellowship, General Electric Foundation
  • 1992-1995
    National Science Foundation Predoctoral Fellowship
  • 1995-1997
    National Institutes of Health Traineeship
  • 1997-1999
    Daymon Runyon-Walter Winchell Cancer Research Postdoctoral Fellowship
  • 2010
    Keynote address, Drug Discovery Chemistry, Protein-Protein Interactions (San Diego)
  • 2012
    Keynote speaker, EFMC-ISMC (Berlin)
  • 2013
    Keynote speaker, PPI-NET (London)
  • 2013
    Finalist, SLAS Innovation Award

Selected Publications

  1. Chin MY, Ang KH, Davies J, Alquezar C, Garda VG, Rooney B, Leng K, Kampmann M, Arkin MR, Kao AW. Phenotypic Screening Using High-Content Imaging to Identify Lysosomal pH Modulators in a Neuronal Cell Model. ACS Chem Neurosci. 2022 May 06.  View on PubMed
  2. Theofilas P, Piergies AMH, Oh I, Lee YB, Li SH, Pereira FL, Petersen C, Ehrenberg AJ, Eser RA, Ambrose AJ, Chin B, Yang T, Khan S, Ng R, Spina S, Seeley WW, Miller BL, Arkin MR, Grinberg LT. Caspase-6-cleaved tau is relevant in Alzheimer's disease and marginal in four-repeat tauopathies: diagnostic and therapeutic implications. Neuropathol Appl Neurobiol. 2022 May 04; e12819.  View on PubMed
  3. Hulce KR, Jaishankar P, Lee GM, Bohn MF, Connelly EJ, Wucherer K, Ongpipattanakul C, Volk RF, Chuo SW, Arkin MR, Renslo AR, Craik CS. Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine. Cell Chem Biol. 2022 May 19; 29(5):785-798.e19.  View on PubMed
  4. Kim GJ, Mo H, Liu H, Okorie M, Chen S, Zheng J, Li H, Arkin M, Huang B, Guo S. In Vivo Dopamine Neuron Imaging-Based Small Molecule Screen Identifies Novel Neuroprotective Compounds and Targets. Front Pharmacol. 2022; 13:837756.  View on PubMed
  5. Kim GJ, Mo H, Liu H, Wu Z, Chen S, Zheng J, Zhao X, Nucum D, Shortland J, Peng L, Elepano M, Tang B, Olson S, Paras N, Li H, Renslo AR, Arkin MR, Huang B, Lu B, Sirota M, Guo S. A zebrafish screen reveals Renin-angiotensin system inhibitors as neuroprotective via mitochondrial restoration in dopamine neurons. Elife. 2021 09 22; 10.  View on PubMed
  6. Chin MY, Patwardhan AR, Ang KH, Wang AL, Alquezar C, Welch M, Nguyen PT, Grabe M, Molofsky AV, Arkin MR, Kao AW. Genetically Encoded, pH-Sensitive mTFP1 Biosensor for Probing Lysosomal pH. ACS Sens. 2021 06 25; 6(6):2168-2180.  View on PubMed
  7. Sijbesma E, Hallenbeck KK, Andrei SA, Rust RR, Adriaans JMC, Brunsveld L, Arkin MR, Ottmann C. Exploration of a 14-3-3 PPI Pocket by Covalent Fragments as Stabilizers. ACS Med Chem Lett. 2021 Jun 10; 12(6):976-982.  View on PubMed
  8. Espinosa JA, Pohan G, Arkin MR, Markossian S. Real-Time Assessment of Mitochondrial Toxicity in HepG2 Cells Using the Seahorse Extracellular Flux Analyzer. Curr Protoc. 2021 Mar; 1(3):e75.  View on PubMed
  9. Chin MY, Espinosa JA, Pohan G, Markossian S, Arkin MR. Reimagining dots and dashes: Visualizing structure and function of organelles for high-content imaging analysis. Cell Chem Biol. 2021 03 18; 28(3):320-337.  View on PubMed
  10. Tyagi R, Bulman CA, Cho-Ngwa F, Fischer C, Marcellino C, Arkin MR, McKerrow JH, McNamara CW, Mahoney M, Tricoche N, Jawahar S, Janetka JW, Lustigman S, Sakanari J, Mitreva M. An Integrated Approach to Identify New Anti-Filarial Leads to Treat River Blindness, a Neglected Tropical Disease. Pathogens. 2021 Jan 14; 10(1).  View on PubMed
  11. Chen S, Suzuki BM, Dohrmann J, Singh R, Arkin MR, Caffrey CR. A multi-dimensional, time-lapse, high content screening platform applied to schistosomiasis drug discovery. Commun Biol. 2020 12 21; 3(1):747.  View on PubMed
  12. Antonia MH Piergies, Panos Theofilas, Cathrine Petersen, Alexander J Ehrenberg, Song Li, Dulce Ovando Morales, Rana A Eser, Teddy Yang, Shireen Khan, Brian Chin, Raymond Ng, Michelle Arkin, Lea Tenenholz Grinberg. Caspase-6-mediated tau cleavage and pathology in Alzheimer’s disease and other tauopathies. Alzheimer's & Dementia. 2020 Dec 7; 16(S3).  View on PubMed
  13. Pohan G, Espinosa JA, Chen S, Ang KK, Arkin MR, Markossian S. Multiparametric High-Content Assays to Measure Cell Health and Oxidative Damage as a Model for Drug-Induced Liver Injury. Curr Protoc Chem Biol. 2020 12; 12(4):e90.  View on PubMed
  14. Sijbesma E, Somsen BA, Miley GP, Leijten-van de Gevel IA, Brunsveld L, Arkin MR, Ottmann C. Fluorescence Anisotropy-Based Tethering for Discovery of Protein-Protein Interaction Stabilizers. ACS Chem Biol. 2020 12 18; 15(12):3143-3148.  View on PubMed
  15. Abdel Aziz MH, Fan Y, Liu L, Moasser MM, Fu H, Jura N, Arkin MR. Expression and purification of active human kinases using Pichia pastoris as a general-purpose host. Protein Expr Purif. 2021 03; 179:105780.  View on PubMed
  16. Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza-Acevedo R, Tognatta R, Yan Z, Pfaff SJ, Machado MR, Bedard C, Coronado PER, Jiang X, Wang J, Pleiss MA, Green AJ, Zamvil SS, Pico AR, Bruneau BG, Arkin MR, Akassoglou K. Author Correction: Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation. Nat Immunol. 2020 Sep; 21(9):1135.  View on PubMed
  17. Blay V, Tolani B, Ho SP, Arkin MR. High-Throughput Screening: today's biochemical and cell-based approaches. Drug Discov Today. 2020 10; 25(10):1807-1821.  View on PubMed
  18. Leandro J, Khamrui S, Wang H, Suebsuwong C, Nemeria NS, Huynh K, Moustakim M, Secor C, Wang M, Dodatko T, Stauffer B, Wilson CG, Yu C, Arkin MR, Jordan F, Sanchez R, DeVita RJ, Lazarus MB, Houten SM. Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex. ACS Chem Biol. 2020 08 21; 15(8):2041-2047.  View on PubMed
  19. Guillory X, Wolter M, Leysen S, Neves JF, Kuusk A, Genet S, Somsen B, Morrow JK, Rivers E, van Beek L, Patel J, Goodnow R, Schoenherr H, Fuller N, Cao Q, Doveston RG, Brunsveld L, Arkin MR, Castaldi P, Boyd H, Landrieu I, Chen H, Ottmann C. Fragment-based Differential Targeting of PPI Stabilizer Interfaces. J Med Chem. 2020 07 09; 63(13):6694-6707.  View on PubMed
  20. Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza-Acevedo R, Tognatta R, Yan Z, Pfaff SJ, Machado MR, Bedard C, Rios Coronado PE, Jiang X, Wang J, Pleiss MA, Green AJ, Zamvil SS, Pico AR, Bruneau BG, Arkin MR, Akassoglou K. Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation. Nat Immunol. 2020 05; 21(5):513-524.  View on PubMed

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